DESCRIPTION: (Applicant's abstract) Structural analysis of the human genome is progressing rapidly, but functional characterization of genes defined in sequencing projects has not kept pace. The goal of this project is to narrow this gap using genomic analysis in zebrafish. Because it is straightforward to make mutations in zebrafish that affect developmental, behavioral, and physiological traits shared by fish and humans, zebrafish can serve as a model for a wide variety of human inherited diseases. The long-term goal of this project is to create a zebrafish gene map that will enhance the comparative and functional analysis of the vertebrate genome. By genetically mapping 4000 zebrafish genes in a homozygous diploid mapping panel this project will fuel the discovery of gene functions by using map information to link DNA sequences with zebrafish mutations, which define essential genes likely to be conserved in all vertebrates. In addition, genes are uniquely suited markers for comparative genomics. Previous analysis identified large chromosomal segments conserved between zebrafish and mammalian genomes. This project will comprehensively chart the correspondence between zebrafish and human genomes by identifying the boundaries of conserved chromosomal segments and defining gene order within these segments. This information will accelerate gene mapping in zebrafish by facilitating comparison with the gene-rich maps of mouse and human. Reciprocally, this project will enhance functional genomics in humans by identifying relationships between mutated genes in zebrafish and their mammalian counterparts. This project has three main aims. (1) 500 SSLP markers will be used to generate a framework map in a homozygous diploid mapping panel. Many thousands of additional markers can be assayed in this panel, so this project will allow creation of a very dense genetic map that can be easily integrated with other zebrafish mapping efforts. (2) 4000 zebrafish genes defined by cDNA and EST sequences in public databases will be mapped in the homozygous diploid panel. These genes will serve as candidates for mutations and will also identify conserved chromosomal regions. (3) Informatics resources will be implemented to streamline data management and allow rapid public access to the map information generated by this project via a WWW interface.